ur aims are to define the structure, evolution and rganization of rabbit immunoglobulin genes and the analogous ene families that encode antigen-specific receptors of rabbit cells. We seek to understand the mechanisms that regulate ene expression during lymphoid cell differentiation. ur comparisons of Basilea, b4, b5 and b9 cDNA sequences llowed us to construct an evolutionary tree in which the rimordial Lagomorph kappa gene had a bas-like (K2) sequence. tructural genes encoding the K1 and K2 constant region sotypes have been identified on Southern blots of genomic DNAs f b5, b9 and bas rabbits. Deletions that occur in the ntervening DNA sequence between the J cluster and CKappa in silent" K2 genes of b4 rabbits appear to also occur in the DNA f bas rabbits that express the K2 gene, although small ifferences could not be detected by our technique. n important and unanticipated level at which the expression nd function of rabbit Kappa chains may be affected is the ncoded protein itself. The locations and total numbers of ysteines affect the light chains' conformation and expression nd may have a similar effect on analogous T cell receptor tructures. Labeled cDNA encoding the putative Beta chain of he mouse T cell receptor, cross-hybridized to rabbit thymus RNA. cDNAs prepared from this mRNA and clones of genomic DNA hat also contain cross-hybridizing sequences are currently nder study. short restriction enzyme fragment from the first framework egion of a VHa2 cDNA clone specifically hybridized to xpressed mRNAs of VHa2 rabbits and not to those of VHa1 and Ha3 rabbits. About 10% of the phage plaques in a genomic ibrary of VHa3 DNA, that were positive with a long VH probe, ere positive with the short probe. Two different 8 kb ubclones, selected from two different positive phage, ontained at least two VH genes. In contrast with mouse VH enes which are usually 8-14 kb apart, these rabbit VH genes re only about 3 kb apart. Studies that are still in progress hus far indicate that all rabbits probably do not have the ame genomic content of structural genes for the complex VHa llotypes.